RT Journal Article
SR Electronic
T1 Nicotinic acetylcholine receptor binding of [F-18]Nifene in the rhesus monkey
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1183
OP 1183
VO 52
IS supplement 1
A1 Ansel Hillmer
A1 Dustin Wooten
A1 Jeff Moirano
A1 Jonathan Engle
A1 Todd Barnhart
A1 Robert Nickles
A1 Dhanabalan Murali
A1 Mary Schneider
A1 Jogeshwar Mukherjee
A1 Bradley Christian
YR 2011
UL http://jnm.snmjournals.org/content/52/supplement_1/1183.abstract
AB 1183 Objectives The agonist [F-18]Nifene (NIF) is a PET radioligand developed to image α4β2 nicotinic acetylcholine receptors (nAChR). This work aims to assess the in vivo imaging characteristics of NIF in rhesus monkeys for the development of PET experiments for nACHR assay. Methods Dynamic PET imaging experiments with NIF were acquired in 4 anesthetized macaca mulatta (rhesus) monkeys using a microPET P4 scanner. Acquisition was initiated with a bolus injection of 3 ± 0.5 mCi of NIF. An injection of (-)-nicotine (0.03 mg/kg, i.v.) was given 45-60 minutes post injection to measure the displacement of NIF receptor binding. A second injection of NIF was given after 30 minutes to measure NIF nondisplaceable uptake. Time activity curves were extracted in the high uptake areas of the thalamus and lateral geniculate region (LG), and the cerebellum for the measurement of target-to-cerebellum ratios (T/C). Results High specific binding was observed in the thalamus and LG. T/C reached a plateau at 25-30 minutes post injection with values of 3.0, 2.4, 3.3, 3.1 for the thalamus, and 2.5, 2.2, 3.0, 2.6 for the LG. Elevated binding of NIF was observed in the subiculum, insular cortex, temporal cortex, and cingulate gyrus. The (-)-nicotine completely displaced NIF, with uptake falling to background levels within 15 minutes post-drug. Negligible displacement of NIF was observed in the cerebellum, suggesting potential as a reference region. Logan DVR estimates using the cerebellum yielded values of 2.8, 2.7, 3.0, 2.8 in the thalamus, and 2.3, 2.3, 2.3, 2.4 in the LG. The post-nicotine injection displayed uniform nondisplaceable uptake of NIF throughout gray and white brain matter. Conclusions In the rhesus monkey, [F-18]Nifene exhibits high specific binding and rapid equilibration in the thalamus and LG. Future work is ongoing to evaluate the behavior of NIF in arterial plasma. These results suggest NIF shows great promise for assessing nACHR binding. Research Support CA143188, AA01770